The 2020 ESPINA study follow-up Exam: Fungicides, Insecticides, Inflammation and Child Development

2020年ESPINA研究后续考试：杀菌剂、杀虫剂、炎症和儿童发育

• 批准号: 10265315
• 负责人: Jose Ricardo Suarez
• 金额: $ 52万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-18 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10265315
• 关键词: Acetylcholinesterase; Adolescence; Adolescent; Affect; Age; Agriculture; Americas; Antifungal Agents; Azoles; Biological Markers; Blood; CCL2 gene; Child; Child Development; Child Health; Cholinesterase Inhibitors; Cognition; Cognitive; County; Cytochrome P450; Cytokeratin 18; Data Collection; Development; Disease; Drug Metabolic Detoxication; Ecuador; Environmental Health; Enzymes; Epigenetic Process; Exposure to; Fatty Liver; Flowers; Follow-Up Studies; Food; Free Radicals; Funding; Future; Gender; Hair; Health; Hepatotoxicity; Human; Impairment; In Vitro; Industrial fungicide; Inflammation; Insecticides; Interleukin-6; Investigation; Link; Liver; Measurement; Measures; Mediating; Mental Health; Methods; Microtubules; National Institute of Environmental Health Sciences; Nerve Degeneration; Neurocognition; Neurocognitive; Neurocognitive Deficit; Neurons; Organophosphates; Outcome; Participant; Patients; Performance; Pesticides; Pharmaceutical Preparations; Physiological; Plasma; Population; Prevention program; Process; Production; Prospective Studies; Quinones; Recurrence; Research; Risk Assessment; Safety; Sales; Saliva; Sampling; Serum; Specimen; Structure; TNF gene; Technology; Testing; Time; Toxic effect; Transaminases; United States National Institutes of Health; Urine; Vascular Endothelium; Work; agricultural community; agricultural pesticide; biobank; clinical practice; cognitive performance; cohort; developmental toxicity; disorder prevention; epidemiology study; experimental study; exposure pathway; follow-up; fruits and vegetables; individuals with autism spectrum disorder; inflammatory marker; inhibitor/antagonist; liver inflammation; monocyte; neurobehavior; neurobehavioral; neuroinflammation; neurotoxic; novel; pesticide exposure; prenatal exposure; prospective; prospective test; pyrethroid; study population; urinary; young adult

The sales of agricultural insecticides have steadily risen in the last 20 years and the use of fungicides have skyrocketed in the last decade. Unfortunately, direct assessments of children's developmental toxicity in relation to commonly used fungicides such as Azoles or Quinone Outside Inhibitors (QoI) are unavailable because methods for their quantification in bio-specimens have only recently been developed. In experimental studies, exposures QoI fungicides, resulted in epigenetic changes related to neuro-inflammation, and higher levels of free-radicals. Azoles, another heavily used fungicide class, have also been linked with liver inflammation and toxicity in-vitro. Azole fungicides share the same structure as azole antifungals used in clinical practice, which are associated with elevations of liver enzymes in up to 20% of patients. Cholinesterase inhibitor insecticide exposures have been associated with short- and long-lasting neurobehavioral/cognitive delays in children associated. Whether continuing exposures to organophosphates or other insecticides such as neonicotinoids or pyrethroids can affect cognition in adolescence is unclear. We propose to conduct a follow-up investigation of adolescent participants (ages 16-21 y, n=535) of the Secondary Pesticide Exposure among Children and Adolescents (ESPINA) study in 2020. This NIH-funded study has examined participants in Pedro Moncayo County, Ecuador since 2008. Pedro Moncayo has one of the highest concentrations of flower plantations in the Americas. The production of flowers involves a disproportionately high use of fungicides. We plan to assess the ongoing and long-term associations of pesticide exposures with neurocognition, and inflammatory markers (systemic, neuro and liver). To our knowledge, this will be the first epidemiologic study of children/adolescents to evaluate health outcomes in relation to fungicide and neonicotinoid exposures. This prospective study capitalizes on existing blood measurements of insecticides in 2016 and acetylcholinesterase in 2008 and 2016. The specific aims are to test the following hypotheses: Urinary metabolites of insecticides in 2016 and 2020 (organophosphates, neonicotinoids, pyrethroids) and fungicides (Azoles, QoI) in 2016 are associated with: 1) higher subclinical markers of systemic and neuro inflammation (CRP, TNF, IL-6, sICAM-1, sVCAM-1, MCP-1, sCD14, sCD163); 2) Pesticides, particularly azole fungicides are associated with subclinical increases in liver inflammation markers: transaminases (AST and ALT) and cytokeratin 18. We will test concurrent and prospective associations with all inflammation markers in 2016-2018; 3) lower neur0-cognitive performance in adolescence. We will test longitudinal associations of fungicides and insecticides with neurocognitive performance, and will contrast such findings across pesticides to evaluate neurotoxic potencies. 4) As an exploratory aim: we will assess mediating or modifying effects of inflammation on pesticide-induced impaired neurobehavioral performance.

在过去的20年里，农业杀虫剂的销售和杀菌剂的使用稳步上升